This clear-cut effect was seen in the communities randomised
to receive these interventions and treatment according to national guidelines,
but as those guidelines changed to treatment-for-all early on in the life of
the trial, the researchers believe it still provides evidence of the efficacy
of the universal test and treat approach.

“Taken together with the findings of other studies, our
results provide key evidence that the universal test and treat strategy can
bring down incidence of new HIV infections, even in settings with severe
generalised HIV epidemics,” Professor Richard Hayes of the London School of
Hygiene and Tropical Medicine told a press conference.

PopART, also known as HPTN 071, was a large
community-randomised trial carried out in Zambia and KwaZulu-Natal, South
Africa. The study aimed to measure the impact on HIV incidence of
household-based HIV testing and linkage to care by community health workers
(lay counsellors) and immediate initiation of antiretroviral treatment
delivered through routine health care services.

PopART was an important test of the feasibility of offering
testing and treatment at a very large scale, essential for achievement of the
90-90-90 target of 90% diagnosed, 90% of diagnosed people on treatment and 90%
of those on treatment virally suppressed. It is the largest HIV prevention
trial ever done: around a million people live in the 21 urban communities in
Zambia and South Africa where it was conducted.

While there have been several large trials of the ‘test and
treat’ approach in African countries in recent years, their results have been
mixed. The ANRS
12249 Treatment as Prevention study showed that a massive scale-up of HIV
testing was feasible, but linkage to care was slow and there was no benefit in
terms of HIV incidence. SEARCH
offered HIV testing alongside screening for non-communicable diseases and achieved
very high rates of HIV diagnosis and viral suppression, but not an overall
effect on HIV incidence. The Botswana
Community Prevention Project led to a 30% drop in HIV infections, although
this was of borderline statistical significance.

The intervention

The researchers developed a comprehensive intervention to
support HIV testing and linkage to care. This involved community health workers
systematically visiting all households within a geographical area and offering
home-based HIV testing and counselling. Individuals found to be HIV positive
were referred to government health clinics for immediate HIV treatment,
regardless of CD4 cell count. Support was also offered for adherence, retention
in care, HIV prevention, STI screening, TB screening, and male circumcision.

The community health workers returned to households
throughout the year as necessary to follow up on referrals and linkages to
care, and to offer HIV testing to household members who were absent at previous
visits or who had declined testing. Hayes emphasised that this was a trial of
universal testing, linkage to care and treatment – not just of
universal treatment.

In this cluster randomised trial, the unit of randomisation
was a geographical community. The 21 urban communities were clustered into
seven groups of three with similar features and similar HIV prevalence. Within
each cluster, one community was randomised to study arm A, one to study arm B
and one to study arm C.

Arm B: the comprehensive
intervention, with ART initiation according to national guidelines.

Arm C: standard of care provision
through routine health services, with ART initiation according to national
guidelines.

As in other ‘test and treat’ trials, this study design was made
less clear-cut by shifting global recommendations concerning when people should
start HIV treatment. When the study opened at the tail end of 2013, the Zambian
and South African guidelines were recommending ART below CD4 cell counts of 350
copies/mm3. But within a few months, that level was raised to 500
copies/mm3. In late 2015, the World Health Organization recommended
universal treatment, regardless of CD4 count, and this was implemented at the
Zambian and South African trial sites in early and late 2016 respectively.

In terms of evaluating the impact of the intervention, the
key data were collected between mid-2015 to mid-2018. Due to the guideline
changes, for two of these three years, there was no difference at all between
arms A and B. In addition, people in arm C were also receiving universal
treatment, but not universal testing.

So it would seem that the results in arm B can tell us about
a universal test and treat approach, even if it was not designed to do so.

To measure the impact of the intervention, the researchers
recruited a random sample of 48,301 adults from the overall study population
(described as the ‘population cohort’). The study’s primary outcome was changes
in HIV incidence (new infections) at the population cohort’s month 12 and month
36 visits, which occurred between mid-2015 and mid-2018. A different team of
research workers made annual visits to test these individuals for HIV, without
offering the comprehensive package of interventions.

Those in the population cohort were predominantly young (39%
were aged 18 to 24) and female (71%). Men were often away from home for work
and it was hard to enrol them, despite repeated visits. At baseline, only
around 55% of those living with HIV were virally suppressed.

Results

There were 553 new HIV infections
in 39,702 person years of follow-up.

Annual incidence was 1.45% in arm
A, 1.06% in arm B and 1.55% in arm C.

Incidence was lower in each of the seven B communities than
in its matched C community. Hayes said that such a consistent result is rarely
seen in cluster randomised trials and is highly unlikely to be due to chance.

The lower incidence in arm B was most notable among women
and people over the age of 25.

The researchers say it is puzzling that incidence was
significantly lower in arm B (which received the comprehensive intervention and
ART according to national guidelines), but not in arm A (which received the
comprehensive intervention and universal ART throughout). They were expecting
similar results in these two arms. If anything, a greater reduction in
incidence should have been seen in arm A, which had universal treatment
throughout the study, rather than for most of it.

What could explain the better results in arm B than in arm
A? There is no evidence of sub-optimal implementation of the intervention in
arm A. In fact, levels of viral suppression were higher (72%) in arm A than arm
B (68%) and arm C (60%).

In the coming months, the researchers will explore possible
causes. There is plenty of evidence in southern Africa that migration raises
risks for HIV and it is possible that some of the communities randomised to arm
A happened to have more mobile populations. Phylogenetic analysis of viral
strains in the population may identify transmission clusters that could help
explain the results. It is also possible that there were differences in sexual
risk behaviour between the arms – data on STIs may
shed light on this. But the result could simply be an unlikely
chance occurrence.

“We found very strong evidence of an effect in the group
that received treatment according to national guidelines,” said Professor
Hayes. “The absence of a clear reduction in HIV incidence in the group that
received the most intensive HIV prevention intervention is surprising and
inconsistent with the group's rate of viral suppression. Further analyses of
qualitative and quantitative data from the study communities may help us better
understand this unexpected result.”

During questions and answers, he said that the team had
conducted a post-hoc analysis which combined arms A and B, in comparison with arm
C. This showed a statistically significant 20% reduction in HIV incidence.

“The overall evidence for the effectiveness of the
intervention is strong,” Hayes said. “Community-based services for universal
HIV testing and linkage to care are a key component of combination prevention
in the global effort to achieve effective HIV control.”

NAM’s information is intended to support, rather than replace, consultation with a healthcare professional. Talk to your doctor or another member of your healthcare team for advice tailored to your situation.

The Community Consensus Statement is a joint initiative of AVAC, EATG, MSMGF, GNP+, HIV i-Base, the International HIV/AIDS Alliance, ITPC and NAM/aidsmap

close

This content was checked for accuracy at the time it was written. It may have been superseded by more recent developments. NAM recommends
checking whether this is the most current information when making decisions that may affect your health.

NAM’s information is intended to support, rather than replace, consultation with a healthcare professional. Talk to your doctor or another member
of your healthcare team for advice tailored to your situation.